LILRB1-based chimeric antigen receptor

Abstract

Provided are chimeric antigen receptors having the hinge, transmembrane region, and/or intracellular domain of LILRB1, or functional fragments or variants thereof. Also provided herein are cells comprising the LILRB1 based receptors, and methods of making and using same.

What is claimed is: 
     
       1. A chimeric antigen receptor comprising a polypeptide comprising:
 a) an antigen binding domain comprising an scFv comprising a CDR-L1, a CDR-L2, a CDR-L3, a CDR-H1, a CDR-H2, and a CDR-H3, wherein
 i) the CDR-L1 comprises SEQ ID NO: 22, the CDR-L2 comprises SEQ ID NO: 23, the CDR-L3 comprises SEQ ID NO: 24, the CDR-H1 comprises SEQ ID NO: 25, the CDR-H2 comprises SEQ ID NO: 26, and the CDR-H3 comprises SEQ ID NO: 27; or 
 ii) the CDR-L1 comprises SEQ ID NO: 28, the CDR-L2 comprises SEQ ID NO: 29, the CDR-L3 comprises SEQ ID NO: 30, the CDR-H1 comprises SEQ ID NO: 31, the CDR-H2 comprises SEQ ID NO: 32, and the CDR-H3 comprises SEQ ID NO: 33; 
 
 b) an LILRB1 hinge domain comprising SEQ ID NO: 4, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 93, or a sequence having at least 95% identity thereto; 
 c) a transmembrane domain comprising SEQ ID NO: 5 or a sequence having at least 95% identity thereto; and 
 d) an LILRB1 intracellular domain comprising at least one immunoreceptor tyrosine-based inhibitory motif (ITIM) selected from the group consisting of NLYAAV (SEQ ID NO: 8), VTYAEV (SEQ ID NO: 9), VTYAQL (SEQ ID NO: 10), and SIYATL (SEQ ID NO: 11). 
 
     
     
       2. The receptor of  claim 1 , wherein the intracellular domain comprises a sequence at least 95% identical to SEQ ID NO: 7. 
     
     
       3. The receptor of  claim 1 , wherein the LILRB1 hinge and transmembrane comprise a sequence at least 95% identical to SEQ ID NO: 20. 
     
     
       4. The receptor of  claim 1 , wherein the LILRB1 transmembrane and intracellular domain comprise a sequence at least 95% identical to SEQ ID NO: 21. 
     
     
       5. The receptor of  claim 1 , wherein the LILRB1 hinge, transmembrane and intracellular domains comprise a sequence at least 95% identical to SEQ ID NO: 3. 
     
     
       6. The receptor of  claim 1 , wherein the LILRB1 hinge, transmembrane and intracellular domains comprise a sequence at least 95% identical to SEQ ID NO: 2. 
     
     
       7. The receptor of  claim 1 , wherein the LILRB1 hinge, transmembrane and intracellular domains comprise SEQ ID NO: 2. 
     
     
       8. The receptor of  claim 1 , wherein the antigen binding domain specifically binds a HLA-A*02 allele of HLA-A. 
     
     
       9. The receptor of  claim 1 , wherein the scFv comprises a sequence at least 95% identical to SEQ ID NO: 39 or SEQ ID NO: 125. 
     
     
       10. The receptor of  claim 1 , wherein the receptor comprises an amino acid sequence at least 95% identical to SEQ ID NO: 122 or SEQ ID NO: 89. 
     
     
       11. The receptor of  claim 1 , wherein the receptor comprises an amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 89. 
     
     
       12. A polynucleotide comprising a nucleic acid sequence encoding the polypeptide of  claim 1 . 
     
     
       13. A vector comprising the polynucleotide of  claim 12 . 
     
     
       14. An immune cell comprising the receptor of  claim 1 . 
     
     
       15. The immune cell of  claim 14 , wherein the immune cell is a T cell. 
     
     
       16. The immune cell of  15 , further comprising an activator receptor.